Dosing Tips

• Has conventional antipsychotic properties at originally recommended doses (i.e., starting at 10 mg twice a day, maintenance 60–100 mg/day, maximum 250 mg/day given in 2 divided doses)

✽ Binding studies, PET studies, and anecdotal clinical observations suggest that loxapine may be atypical at lower doses (perhaps 5–30 mg/day) but further studies needed

• Anecdotal evidence that many patients can be maintained at 20–60 mg/day as monotherapy

• To augment partial responders to an atypical antipsychotic, consider doses of loxapine as low as 5–60 mg/day, but use full doses if necessary

• No formal studies, but some patients may do well on once daily dosing, especially at night, rather than twice daily dosing

• Available as 5-mg and 10-mg capsules for low-dose use and as 25-mg and 50-mg capsules for routine use

• Available as a liquid dosage formulation

• Available for acute inhalation administration

• Prior to administering inhalation powder, screen all patients for a history of pulmonary disease, and examine patients (including chest auscultation) for respiratory abnormalities (e.g., wheezing)

• After administering inhalation powder, monitor patients for signs and symptoms of bronchospasm at least every 15 minutes for at least an hour

• Available for acute intramuscular administration (50 mg/mL)

• Intramuscular loxapine may have faster onset of action and superior efficacy for agitated/excited and aggressive behavior in some patients than intramuscular haloperidol

• In the acute situation, give 25–50 mg intramuscularly (0.5–1.0 mL of 50 mg/mL solution) with onset of action within 60 minutes

• When initiating therapy with an atypical antipsychotic in an acute situation, consider short-term intramuscular loxapine to “lead in” to orally administered atypical; e.g., initiate oral dosing of an atypical antipsychotic with 25–50 mg loxapine 2–3 times a day intramuscularly to achieve antipsychotic effects without extrapyramidal symptoms and sedation

• When using loxapine to “top-up” previously stabilized patients now decompensating, may use loxapine as single 25–50 mg doses as needed intramuscularly or as oral liquid or tablets

• Patients receiving atypical antipsychotics may occasionally require a “top up” of a conventional antipsychotic to control aggression or violent behavior

• Treatment should be suspended if absolute neutrophil count falls below 1,000/mm³

Overdose

• Deaths have occurred; extrapyramidal symptoms, CNS depression, cardiovascular effects, hypotension, seizures, respiratory depression, renal failure, coma

Long-Term Use

• Some side effects may be irreversible (e.g., tardive dyskinesia)

Habit Forming

• No

How to Stop

• Slow down-titration of oral formulation (at least 4 weeks when possible), especially when simultaneously beginning a new antipsychotic while switching (i.e., cross-titration)

• Rapid oral discontinuation may lead to rebound psychosis and worsening of symptoms

• If antiparkinson agents are being used, they should be continued for a few weeks after loxapine is discontinued

Pharmacokinetics

• Half-life approximately 4 hours for oral formulation

• Half-life approximately 12 hours for intramuscular formulation

• Multiple active metabolites with longer half-lives than parent drug

✽ N-desmethyl loxapine is amoxapine, an antidepressant

• 8-hydroxyloxapine and 7-hydroxyloxapine are also serotonin-dopamine antagonists

• 8-hydroxyamoxapine and 7-hydroxyamoxapine are also serotonin-dopamine antagonists